Solubility of a drug is important with respect to drug dissolution rate from a solid dosage form and subsequent bioavailability for systemic absorption.
Where the free acid form of weakly acidic drugs have poor water-solubility, it has been the practice to employ such drugs in the form of their water-soluble salts. The water-soluble salts will generally have good dissolution properties and acceptable bioavailability characteristics.
BMS 180,291, a thromboxane A.sub.2 receptor antagonist, disclosed in U.S. Pat. No. 5,100,889 to Misra et al, has the formula ##STR1## and the name [1S-(1.alpha., 2.alpha.,3.alpha.,4.alpha.)]-2-[[3-[4-[(pentylamino)carbonyl]-2-oxazolyl]- 7-oxabicyclo[2.2.1]hept-2-yl]methyl]benzenepropanoic acid or a pharmaceutically acceptable salt thereof such as its sodium salt, potassium salt, calcium salt or magnesium salt.
For matter of convenience, BMS 180,291 will hereinafter be referred to as "ifetroban".
In its free acid form, ifetroban is poorly water-soluble (ca. 7 mcg/mL). The sodium salt of ifetroban is freely soluble in water (&gt;450 mg/mL) with excellent chemical and physical stability. Initially, capsule and tablet compositions of the sodium salt of ifetroban exhibit good chemical stability and rapid dissolution rate. However, upon storage for two weeks at 30.degree. C., the dissolution rate of these compositions slow down dramatically. This is indeed surprising in view of the excellent chemical stability and high water-solubility of the sodium salt of ifetroban. In fact, it has been found that the sodium salt of ifetroban upon aging, undergoes an acid-base reaction resulting in formation of the free acid form of ifetroban which results in the dissolution rate slowdown.